标题:Relaxation Induced by Atrial Natriuretic Peptide Is Impaired in Carotid but Not Renal Arteries from Spontaneously Hypertensive Rats Due to Reduced BKCa Channel Activity
摘要:Atrial natriuretic peptide (ANP) plays an important role in vascular functions such as blood pressure regulation and relaxant activity. Individual vascular beds exhibit differences in vascular reactivity to various ligands, however, the difference in responsiveness to ANP between carotid and renal arteries and the molecular mechanisms of its vasorelaxant activity in a pathophysiological state, including hypertension, remain unclear. We therefore investigated this issue by exposing carotid and renal artery rings obtained from spontaneously hypertensive rats (SHR) to ANP. In the SHR artery ( vs. control WKY artery), the ANP-induced relaxations were reduced in carotid artery but not renal artery. Acetylcholine-induced relaxations were reduced in both arteries in SHR ( vs. WKY). Sodium nitroprusside-induced relaxation was similar in both arteries between the groups. In carotid arteries, the ANP-induced relaxation was not affected by endothelial denudation or by treatment with inhibitors of nitric oxide synthase, cyclooxygenase, the voltage-dependent potassium channel, or ATP-sensitive potassium channel in arteries from both SHR and WKY. In the carotid artery from WKY but not SHR, the ANP-induced relaxation was significantly reduced by inhibition of the large-conductance calcium-activated potassium channel (BKCa). The BKCa activator-induced relaxation was reduced in the SHR artery ( vs. WKY). These results suggest that ANP-induced relaxation is impaired in the carotid artery from SHR and this impairment may be at least in part due to the reduction of BKCa activity rather than endothelial components.